Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients

Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.

Androgen-independent growth in LNCaP cell lines and steroid uridine diphosphate-glucuronosyltransferase expression

<abstract>Aim: To investigate the mechanism of androgen-independent growth of prostate cancer after androgen ablation in LNCaP cells and the effect of glucuronidation activity. Methods: To establish androgen-independent growth in prostate cancer LNCaP-SF, continuous passage was performed in androgen-stripped medium and the cells were evaluated for glucuronidation activity. The expression vector of antisense uridine diphosphate glucuronosyltransferase (UGT) 2B15 cDNA was also constructed and evaluated. Results: LNCaP-SF lead to a higher expression in UGT2B15 and their glucuronidation activity is 2.5 times higher than that of LNCaP cells. Significantly fewer LNCaP and LNCaP-SF than control were transfected with the antisense UGT2B15 cDNA, suggesting that UGT2B15 plays an important part in the glucuronidation activity of androgens in both cells. Conclusion: The alteration of UGT2B15 expression in LNCaP-SF cells is proposed as a biological characteristic involved in the growth of hormonerefractory prostate cancer.

Inter/intra investigator variation in orchidometric measurements of testicular volume by ten investigators from five institutions

Aim： To perform quality control studies on testicular volume measurements for a multi-center epidemiological study of male reproductive function. Methods： We constructed a data matrix with a balanced assignment for 2 consecutive days by ten investigators （andrological career： 4-21 years） from five institutions and 12 male volunteers aged 20-26 years. Testicular volume was measured by Prader＇s orchidometer. A skilled technician also performed an ultrasound estimate of testicular volume. Results： A statistically significant inter-investigator variation was found for both testes （P 〈 0.05）. In addition, there was a statistically significant investigator-by-volunteer interaction in testicular volume measurement （P 〈 0.01）. However, there was no statistically significant difference in the two measurements performed on consecutive days for either testis. The testicular volumes for both the right and left testes as estimated by ultrasonography were smaller than results using the orchidometer. However, there was no statistical significance （P 〉 0.05）. The difference in experiences of the investigators did not significantly correlate with accuracy of measurements in either testis. Conclusion： The present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.

Preoperative Exercise Testing Is a Better Predictor of Postoperative Complications than Pulmonary Function Testing for Patients with Lung Cancer

Objective: The aim of this preliminary study was to evaluate the feasibility of exercise testing (ET) for predicting postoperative complications in patients with impaired pulmonary function. Methods: Thirteen patients were prospectively enrolled. The enrollment criteria were FEV1.0% 8 by the Goddard classification or interstitial pneumonia on chest computed tomography. Patients underwent testing for pulmonary function, six-minute walking test (6MWT), and stair-climbing test (SCT). Postoperative cardiopulmonary complications (PCPCs) were recorded. Results: Four patients developed PCPCs. There were no significant differences between the patients with PCPCs (n = 4) and those without PCPCs (n = 9) for background data and PFT. The distances achieved in the 6MWT were 503 ± 72.7 m for patients without PCPCs and 369 ± 50.7 m for patients with PCPCs (p = 0.011). The SCT climbing heights were 20.4 ± 5.3 m for patients without PCPCs and 14.9 ± 4.0 m for patients with PCPCs (P = 0.187). Cut-off points, including a 6MFT distance of less than 400 m, SCT height lower than 15 m, and SCT climbing speed less than 8.5 m/min, were predictive of CPCP. Conclusions: Exercise testing is more feasible for predicting postoperative cardiopulmonary complications than stationary pulmonary function testing.

Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism： a multicenter, randomized controlled trial in Japan （EARTH Study）

Androgen replacement therapy （ART） efficacy on late-onset hypogonadism （LOH） has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores （IPSS）, International Index of Erectile Function-5 （IIEF-5） scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients 〉 40 years with LOH were randomly assigned to either the ART （n = 169） or control groups （n = 165）. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey （SF-36） scale （P= 0.0318）. ART was also associated with significant decreases in waist circumstance （P = 0.002） and serum triglyceride （TG） （P = 0.013） and with significant increases in whole-body and leg muscle mass volumes （P= 0.071 and 0.0108, respectively）, serum hemoglobin （P 〈 0.001）, IPSS voiding subscore （P = 0.0418）, and the second question on I IEF-5 （P = 0.0049）. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.